Silent mutation

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Forms of point mutation

A silent mutation (synonymous with silent mutation ) is a mutation in a coding sequence of nucleic acids that does not affect the protein biosynthesis of a newly emerging protein .

properties

A silent mutation is mostly a point mutation through substitution . One nucleotide is exchanged for another. The affected codon is changed, but the encoded amino acid remains the same. A silent mutation with no effects is also known as a neutral mutation . A silent mutation in an exon is called a synonymous mutation . Even a non-synonymous mutation can be a silent mutation if the effect of changing an encoded amino acid is sufficiently low, ie when an amino acid has been replaced by a similar amino acid that has no influence on the functionality of the protein.

However, not every synonymous mutation is a silent mutation. A synonymous mutation can change the secondary structure of an mRNA , which in turn affects the initiation and termination of translation . In the case of a synonymous mutation, the kinetics of the use of the different codons for the same amino acid during translation on the ribosome can have an effect on the protein folding and thus on the secondary and tertiary structure as well as the biological activity of a newly emerging protein and thus also cause a changed phenotype , without that the amino acid sequence changes. Because of the comparatively slow binding of tRNA, some codons are then also slowly translated into an amino acid during translation, which has a corresponding effect on the preferred codon usage as well as on the secondary structure and degradation stability of mRNA. Examples of silent mutations that still affect the phenotype are e.g. B. p-glycoprotein (synonymous MDR1 ) and CFTR , which in some silent mutations lead to incorrect protein folding despite the correct amino acid sequence.

Applications

By codon optimization can gene expression rate increased by only those 20 amino acid codons are used which are most highly expressed in the species. One common use of suboptimal codons is a method of attenuating live viral vaccines that has been demonstrated on poliovirus . In addition, silent mutations are introduced during cloning in order to create new restriction sites for restriction enzymes .

literature

  • Zhang, Miteva MA, Wang L., Alexov E.: Analyzing effects of naturally occurring missense mutations. In: Computational and mathematical methods in medicine. Volume 2012, 2012, p. 805827, doi : 10.1155 / 2012/805827 , PMID 22577471 , PMC 3346971 (free full text).

Web links

Individual evidence

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  3. ↑ JV Chamary, JL Parmley, LD Hurst: Hearing silence: non-neutral evolution at synonymous sites in mammals. In: Nature Reviews Genetics . Volume 7, Number 2, February 2006, pp. 98-108, doi : 10.1038 / nrg1770 , PMID 16418745 .
  4. ↑ Patrick Goymer: Synonymous mutations break their silence. In: Nature Reviews Genetics. 8, 2007, p. 92, doi : 10.1038 / nrg2056 .
  5. ↑ T. Zhou, EA Ko, W. Gu, I. Lim, H. Bang, JH Ko: Non-silent story on synonymous sites in voltage-gated ion channel genes. In: PLOS ONE . Volume 7, number 10, 2012, p. E48541, doi : 10.1371 / journal.pone.0048541 , PMID 23119053 , PMC 3485311 (free full text).
  6. ↑ SA Shabalina, AY Ogurtsov, NA Spiridonov: A periodic pattern of mRNA secondary structure created by the genetic code. In: Nucleic acids research. Volume 34, number 8, 2006, pp. 2428-2437, doi : 10.1093 / nar / gkl287 , PMID 16682450 , PMC 1458515 (free full text).
  7. ^ Mary K. Campbell: Biochemistry. Cengage Learning, 2016, ISBN 978-1-337-51435-4 , p. 391.
  8. ↑ Czech A, Fedyunin I, Zhang G, Ignatova Z: Silent mutations in sight: co-variations in tRNA abundance as a key to unravel consequences of silent mutations . In: Mol Biosyst . 6, No. 10, October 2010, pp. 1767-72. doi : 10.1039 / c004796c . PMID 20617253 .
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  12. ↑ a b C. Kimchi-Sarfaty, JM Oh, I.-W. Kim, ZE Sauna, AM Calcagno, SV Ambudkar, MM Gottesman ,: A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity . In: Science . 315, No. 5811, January 26, 2007, pp. 525-8. doi : 10.1126 / science.1135308 . PMID 17185560 .
  13. ↑ Angov E: Codon usage: nature's roadmap to expression and folding of proteins . In: Biotechnol J . 6, No. 6, June 2011, pp. 650-9. doi : 10.1002 / biot.201000332 . PMID 21567958 . PMC 3166658 (free full text).
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  15. ↑ E. Kotsopoulou, VN Kim, AJ Kingsman, SM Kingsman, KA Mitrophanous: A Rev-independent human immunodeficiency virus type 1 (HIV-1) -based vector that exploits a codon-optimized HIV-1 gag-pol gene. In: J Virol. (2000), Vol. 74 (10), pp. 4839-52. PMID 10775623 ; PMC 112007 (free full text).
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